The overall objective of this project is the design and development of a novel class of human immunodeficiency virus (HIV) vaccines that are synthetic, peptide-based, containing multiple-antigen, carrier-free, and with built-in adjuvant. Such a novel synthetic vaccine is aimed at improving the problems of conjugation, carrier, and adjuvant found in synthetic vaccines. THe proposed design will contain multiple peptide antigens related to HIV such as T helper-inducing determinants and B-cell determinants as well as an adjuvant, all attaching to a small, dendritic branching lysyl core known as the multiple antigen peptide (MAP) system developed recently in our laboratory. Furthermore, the peptide antigens and the lysyl core will be arranged precisely as a single unit and synthesized in a chemically unambiguous manner. In addition, the MAP system contains a high density of peptide antigens on the outer surface (>90% of the total molecular weight) and only a small scaffolding lysyl core (<10% of the molecular weight). These distinct features also serve to overcome the impediment of the carrier problem in the design of peptide-based vaccines. Moreover, the simplicity of the design also provides modifications and developments to enhance both the immunogenicity and long term stability for human vaccines. Finally, fatty acid, liposome-forming or membrane-anchoring moiety conjugated to the MAPs are proposed as suitable models to alleviate the use of adjuvants. Thus, the long term goal of this project is the design and development of a chemical-defined, self-sufficient, multiple-antigen, carrierless, and peptide-based vaccine suitable for humans and protective against human immunodeficiency virus. Although we have demonstrated that the MAP system provides an excellent prototype model in eliciting immunological responses in animals, much of the potentials of the MAP system has yet to be defined. Our immediate goals are (1) to optimize the design of the MAP models, namely; the size, arrangement, stoichiometric relationship of outer peptide antigens and the small branching lysyl core, using selected and known peptide epitopes of the envelop proteins of the human immunodeficiency virus, (2) to incorporate adjuvants in MAPs, and (3) to test and evaluate the efficacy of these models in animals.